This invention relates to low swelling starches suitable for use as tablet disintegrants. It also relates to a method for preparing and characterizing suitable starch powders. It further relates to compressed tablets containing the starch disintegrants and to methods for preparing the tablets by wet granulation, dry granulation, or direct compression.
Tablets usually consist of several inert materials, referred to as excipients, in addition to the active ingredient which is present in amounts sufficient to accomplish the desired pharmaceutical, nutritive, or chemical effect. These excipients are generally classified according to their function, such as diluents (also called bulking agents and fillers), binders which hold the ingredients together, disintegrants which help the tablet to break apart when placed in a fluid environment and thus release the active ingredient, and lubricants to improve the release of the compressed tablet from the die and punches. In addition, the tablets may contain other substances intended to improve the tabletting process. For example, glidants are added to improve the flow and anti-adhesives are added to prevent film formation on the punches. Other optional ingredients may be dyes, flavors, sweeteners, and antioxidants.
The disintegrants are added directly to the dry ingredients when the direct compression tabletting method is used. When the dry or wet granulation tabletting methods are used, the disintegrant may be added before granulation (intragranularly), after granulation (extragranularly), or part may be added intragranularly and part added extrangranulary.
The disintegrants currently used include native starches, modified starches, gums, cellulose derivatives, microcrystalline cellulose, alginates, clays, effervescent mixtures, and enzymes. Of these, the starches, despite some drawbacks, are the formulator's first choice.
Starch as a disintegrant should not be confused with starch as a binder or diluent since different properties are required for each use. Moreover, the properties required in a disintegrant may depend upon the tabletting method used.
The unmodified native starches which are useful as diluents are not very effective when used as disintegrants unless used at high levels (i.e. 10-20%). They swell only very slightly when exposed to water at the temperature found in gastric or intestinal juices. This results in a slight increase in volume which eventually weakens the forces holding the tablet together and thus breaks it apart.
The cooked non-granular starches which are satisfactory as binders are not satisfactory as disintegrants. They can be cooked and added as a paste or gelatinized by drum drying (drum dried starches are often referred to as pregelatinized starches). The cooked or gelatinized starches do not readily disperse; they tend to hydrate rapidly and in many cases form a tacky film on the tablet's surface, thus preventing water penetration into the tablet to aid in disintegration.
Various attempts have been made to modify the cold-water-swelling characteristics of starches to improve their disintegration properties. These have included chemical and physical modification of the starch. Chemical derivatization has produced cold-water-swelling, cold-water-soluble intact granular starches such as starch phosphate, starch sulfate, and carboxymethyl starch (see U.S. Pat. No. 3,034,911 issued May 15, 1962 to I. K. McKee et al.). Physical modification by compaction, with or without the use of supplemental thermal energy, has produced partially cold-water-swelling, cold-water-soluble starches which are claimed to be useful as binder-disintegrants for direct compression tabletting (see respectively U.S. Pat. Nos. 3,622,677 and 4,072,535 issued Nov. 23, 1971 and Feb. 7, 1978 to R. W. P. Short et al.). This physical modification disrupts the granular structure and results in a mixture of birefringent and non-birefringent granules, some aggregates of birefringent and non-birefringent granules and fragments, as well as completely solubilized starch.
It is an object of this invention to provide modified starches which are low swelling in cold water and which are suitable for use as disintegrants in compressed tablets prepared by any tabletting method.